Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2014 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1002/jmv.24015 |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/8464 |
Resumo: | Butantan Institute. Viral Imunology. São Paulo, SP, Brasil / Applied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, Brasil |
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Carvalho, Isabel Maria Vicente Guedes deSilva, Rafael Alves daSouza, Polyana A Vasconcelos Medeiros deSilva, Edvaldo F. daMazo, Daniel Ferraz de CamposCarrilho, Flair JoséQueiroz, Artur Trancoso Lopo dePessoa, Mario Guimarães2014-09-29T13:55:12Z2014-09-29T13:55:12Z2014CARVALHO, I. M. V. G et al. Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. Journal of Medical Virology, v. 86, n. 10, p. 1714-1721, 2014.1096-9071https://www.arca.fiocruz.br/handle/icict/846410.1002/jmv.24015engWiley Periodicals, IncProtease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleButantan Institute. Viral Imunology. São Paulo, SP, Brasil / Applied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, BrasilApplied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, BrasilButantan Institute. Viral Imunology. São Paulo, SP, Brasil / Applied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, BrasilUniversity of São Paulo School of Medicine. Department of Gastroenterology. São Paulo, SP, BrasilUniversity of São Paulo School of Medicine. Department of Gastroenterology. São Paulo, SP, BrasilUniversity of São Paulo School of Medicine. Department of Gastroenterology. São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversity of São Paulo School of Medicine. Department of Gastroenterology. São Paulo, SP, BrasilSeveral new direct-acting antiviral (DAA) drugs are being developed or are already approved for the treatment of chronic hepatitis C virus (HCV) infection. HCV variants presenting drug-resistant phenotypes were observed both in vitro and during clinical trials. The aim of this study was to characterize amino acid changes at positions previously associated with resistance in the NS3 protease in untreated Brazilian patients infected with HCV genotypes 1a and 1b. Plasma samples from 171 untreated Brazilian patients infected with HCV were obtained from the Department of Gastroenterology of Clinics Hospital (HCFMUSP) in São Paulo, Brazil. Nested PCR and Sanger sequencing were used to obtain genetic information on the NS3 protein. Bioinformatics was used to confirm subtype information and analyze frequencies of resistance mutations. The results from the genotype analysis using non-NS3 targeted methods were at variance with those obtained from the NS3 protease phylogenetic analyses. It was found that 7.4% of patients infected with HCV genotype 1a showed the resistance-associated mutations V36L, T54S, Q80K, and R155K, while 5.1% of patients infected with HCV genotype 1b had the resistance-associated mutations V36L, Q41R, T54S, and D168S. Notably, codons at positions 80 and 155 differed between samples from Brazilian patient used in this study and global isolates. The present study demonstrates that genotyping methods targeting the NS3 protein showed a difference of results when compared to mainstream methodologies (INNO-LiPA and polymerase sequencing). The resistance mutations present in untreated patients infected with HCV and codon composition bias by geographical location warrant closer examination.HCVHepatitis CProtease inhibitorsResistanceGenotypinginfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8464/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALCarvalho IMVG Protease inhibitor....pdfCarvalho IMVG Protease inhibitor....pdfapplication/pdf1106740https://www.arca.fiocruz.br/bitstream/icict/8464/2/Carvalho%20IMVG%20Protease%20inhibitor....pdfb46c977078fa7e9aafa08ccb325a33e4MD52TEXTCarvalho IMVG Protease inhibitor....pdf.txtCarvalho IMVG Protease inhibitor....pdf.txtExtracted texttext/plain35482https://www.arca.fiocruz.br/bitstream/icict/8464/3/Carvalho%20IMVG%20Protease%20inhibitor....pdf.txt47ea496d91de4276e6b2f8d68387996dMD53icict/84642023-03-15 14:33:01.771oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:01Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. |
| title |
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. |
| spellingShingle |
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. Carvalho, Isabel Maria Vicente Guedes de HCV Hepatitis C Protease inhibitors Resistance Genotyping |
| title_short |
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. |
| title_full |
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. |
| title_fullStr |
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. |
| title_full_unstemmed |
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. |
| title_sort |
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. |
| author |
Carvalho, Isabel Maria Vicente Guedes de |
| author_facet |
Carvalho, Isabel Maria Vicente Guedes de Silva, Rafael Alves da Souza, Polyana A Vasconcelos Medeiros de Silva, Edvaldo F. da Mazo, Daniel Ferraz de Campos Carrilho, Flair José Queiroz, Artur Trancoso Lopo de Pessoa, Mario Guimarães |
| author_role |
author |
| author2 |
Silva, Rafael Alves da Souza, Polyana A Vasconcelos Medeiros de Silva, Edvaldo F. da Mazo, Daniel Ferraz de Campos Carrilho, Flair José Queiroz, Artur Trancoso Lopo de Pessoa, Mario Guimarães |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Carvalho, Isabel Maria Vicente Guedes de Silva, Rafael Alves da Souza, Polyana A Vasconcelos Medeiros de Silva, Edvaldo F. da Mazo, Daniel Ferraz de Campos Carrilho, Flair José Queiroz, Artur Trancoso Lopo de Pessoa, Mario Guimarães |
| dc.subject.en.pt_BR.fl_str_mv |
HCV Hepatitis C Protease inhibitors Resistance Genotyping |
| topic |
HCV Hepatitis C Protease inhibitors Resistance Genotyping |
| description |
Butantan Institute. Viral Imunology. São Paulo, SP, Brasil / Applied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, Brasil |
| publishDate |
2014 |
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2014-09-29T13:55:12Z |
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2014-09-29T13:55:12Z |
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2014 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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CARVALHO, I. M. V. G et al. Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. Journal of Medical Virology, v. 86, n. 10, p. 1714-1721, 2014. |
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https://www.arca.fiocruz.br/handle/icict/8464 |
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1096-9071 |
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10.1002/jmv.24015 |
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CARVALHO, I. M. V. G et al. Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. Journal of Medical Virology, v. 86, n. 10, p. 1714-1721, 2014. 1096-9071 10.1002/jmv.24015 |
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Wiley Periodicals, Inc |
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Wiley Periodicals, Inc |
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